Do Moonlighting Proteins Belong to the Intrinsically Disordered Protein Class?

Moonlighting proteins refer to those proteins presenting two or more functions performed by a single polypeptide chain. They were initially reported by Wistow and Piatigorsky in the late 1980s when lens crystallins turned out to be previously known metabolic enzymes [1,2]. Moonlighting proteins present alternative functions which are mostly related to cellular localization, cell type, oligomeric state, cellular concentration of ligands, substrates, cofactors, products or post-translational modifications [3-11]. In many cases, a protein uses a combination of these mechanisms to switch between functions. Although some findings suggest involvement of a protein in extra functions, i.e., they can be found in different cellular locations or in amounts exceeding those required for their canonical function. Usually, moonlighting proteins are experimentally revealed by serendipity. Therefore, any alternative method to identify these proteins would be very valuable. In previous works, we have explored the possibility of identifying moonlighting proteins by bioinformatics [12] and protein interactomics-database mining [13].